There are two main objectives to the research outlined in this proposal. The neural processes by which the sex steroid hormones interact to regulate the lordosis component of female rodent sexual behavior will be studied. In addition, the modulation of steroid hormone sensitivity by neurotransmitters in the brain will be investigated. This research involves a multidisciplinary approach which will make use of techniques of endocrinology, behavior, neuroanatomy and neuropharmacology. The experiments in this proposal will add to our understanding of the cellular mechanisms by which the sex steroid hormones act on the central nervous system. Progesterone's effect on lordosis in guinea pigs is used as a model system for these neuroendocrine interactions because progesterone has a unique, biphasic effect on this behavior, and because lordosis is a reliable, easily quantifiable behavioral end-point of hormone action. In gonadectomized female rodents, progesterone synergizes with estradiol and induces a subsequent desensitization to progesterone. The role of the progestin receptor system in mediating progesterone's effects on this behavior, the factors involved in its regulation, and some of the mechanisms involved will be studied. The hypothesis that progesterone's desensitization effect, like its facilitatory effect, is involved in the regulation of sexual behavior during the estrous cycle of rodents will also be tested. Experiments to study the modulation of neural steroid hormone receptors by neurotransmitters are also described. These experiments are designed to determine if norepinephrine influences the concentration of neural steroid hormone receptors, and if so, by which neural pathways. The hypothesis that this regulation has functional significance for behavior will be tested in several ways.